It is estimated that there are more than 250,000 non-CF bronchiectasis patients in the US (SDI Innovations in Healthcare Analytics, 2008), of which approximately 30% of non-CF bronchiectasis patients are infected with Pseudomonas (Wilson, C.B., et al., Eur Respir, 1997, 10(8):1754-1760); Nicotra, M.B., et al., Chest, 1995 108(4):955-961).
Currently there are no approved antibiotics for this indication.
When bronchiectasis patients become infected with Pseudomonas, they tend to have more frequent exacerbations and hospitalizations and are more frequent users of antibiotics.
ARIKACE was granted orphan drug status in the US for the treatment of bronchiectasis in patients with Pseudomonas or other susceptible pathogens.
In May 2009 we completed our randomized, placebo controlled US phase 2 study (TR02-107) of ARIKACE in the treatment of chronic Pseudomonas infection in non-CF patients with bronchiectasis.
In the study, 64 study subjects were randomized (1:1:1) to receive ARIKACE 280 mg, ARIKACE 560 mg or a placebo on a daily basis during a 28-day on-treatment period. The subjects completed follow-up assessments at the end of a 28-day off-treatment period.
There was a statistically significant reduction in Pseudomonas density observed in the 560 mg ARIKACE cohort relative to the placebo cohort.
Patients receiving ARIKACE experienced fewer pulmonary exacerbations at a rate of 4.7%, as compared to 10.5% in those receiving placebo.
No patients in the ARIKACE cohorts required anti-Pseudomonas rescue treatment, whereas 15% of patients in the placebo cohort required treatment.
Hospitalization from any cause occurred at a 5.3% rate for patients in the placebo cohort, as compared to a 2.3% rate for patients in the ARIKACE cohort.
Patients receiving ARIKACE achieved improvements in patient respiratory symptoms and quality of life assessments compared with patients receiving placebo.
"Currently there are no approved antibiotics for this indication".
Yep.... I also expect bronchiectasis to be "the next big thing".
Three weeks ago Pharmaxis (ASX:PSX) failed to meet their Phase III primary endpoint.
too bad ;-)
"We applied for orphan drug designation for NTM infections in the U.S. in 2011. In response to this application, the FDA has requested either in vivo or clinical data in support of our application for orphan drug designation. We plan to file for orphan drug designation for NTM lung infections in the EU after obtaining additional pre-clinical data, which is expected by the end of 2012."
Is it a reasonable assumption that the finding of "no evidence of neoplasia, squamous metaplasia or proliferative changes" in dogs exposed to Arikace every day for nine months was the catalyst for the NTM orphan drug designation?
That third orphan designation offers further reason to believe that the order of importance of the Arikace opportunities is as follows -
1. Severe pneumonia caused by amikacin-susceptible pathogens (including Mycobacterium tuberculosis)
In suggesting "severe" pneumonia rather than any pneumonia as the main Arikace opportunity I reflected the minimum outcome if the FDA now sees fit to approve Arikace for the use originally intended by Transave.
Lewis recently mentioned that the original plan was an approval via the 505(b)(2) pathway, designed for new or improved use of a drug already approved by the FDA (the "reference drug").
The Arikace "reference drug" - amikacin injection - is approved for "the treatment of serious infections due to susceptible strains of Gram-negative bacteria, including Pseudomonas species, Escherichia coli, ... Klebsiella-Enterobacter-Serratia species, and Acinetobacter (Mima-Herellea) species."
Had the FDA allowed Transave to go that route Arikace would presumably have been approved for "the treatment of serious pulmonary infections due to susceptible strains of Gram-negative bacteria".
One assumes the FDA instead classed Arikace as a New Chemical Entity in order to ensure a clinical trial program sufficiently rigorous to generate good visibility on the risks associated with prolonged inhalation of liposomes.
I believe those safety concerns have now been addressed.
And although that original NCE designation disqualified Arikace for a 505(b)(2) approval, the FDA's new powers to counter the threat posed by antimicrobial resistance do include approval based upon "an effect on a surrogate endpoint" -
"The Secretary may approve an application for approval of a product for a serious or life-threatening disease or condition, including a fast track product, under section 505(c) or section 351(a) of the Public Health Service Act upon a determination that the product has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit ..."
Will the FDA view "Change in density in Pseudomonas aeruginosa in sputum" as a surrogate endpoint reasonably likely to predict survival in pneumonia due to susceptible strains of Gram-negative bacteria?